The Glomerular Clearance of Exogenous Insulin[*]

Abstract

The glomerular clearance of insulin was determined according to the method of Moncke and Yuile. Anesthetized dogs maintained in normoglycemia by glucose compensation were infused with crystalline insulin and with ¹²⁵I-insulin (S.A. 1.5-3.0 mCi/mg, mean iodination degree inferior to 0.2 I/Mol.). Plasma insulin levels ranging from 20 µU/ml to 7 U/ml were tested. Creatinine and ¹³¹I-insulin were used to estimate the glomerular filtration rate.

Analysis of the relationship between the urinary outflow of insulin and its plasmatic concentration detected 2 parts in the titration curve: an initial splay extending to plasma levels of 0.3 U/ml followed by a straight line allowing the determination of insulin glomerular clearance.

The comparison between the glomerular clearance rate of insulin and the glomerular filtration rate demonstrated the existence of an important sieving phenomenon, the value of the sieving coefficient averaging 0.58 for crystalline insulin and 0.40 for labelled insulin. These results do not support the concept that exogenous insulin would circulate either as a free monomer (M.W. 6,000) or as bound to plasma proteins but under the form ot a polymer, the sizes of the circulating particles standing between that of myoglobin (M.W. 17,000) and of ovalbumin (M.W. 43,000). The influence of iodination upon the velocity of passage through the glomerular walls is discussed.

The initial splay of the curve probably results from a phenomenon of tubular reabsorption.

Key words

Crystalline Insulin - Labelled Insulin - Mechanism of Proteinuria - Glomerular Clearance - Sieving Coefficient - Tubular Reabsorption - Polymerization of Insulin

1 Communication partially presented at the 8th annual meeting of the European Association for the Study of Diabetes, Madrid 6-8th September 1972.

1 Communication partially presented at the 8th annual meeting of the European Association for the Study of Diabetes, Madrid 6-8th September 1972.